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Large laser facilities have recently enabled material characterization at the pressures of Earth and Super-Earth cores. However, the temperature of the compressed materials has been largely unknown, or solely relied on models and simulations, due to lack of diagnostics under these challenging conditions. Here, we report on temperature, density, pressure, and local structure of copper determined from extended x-ray absorption fine structure and velocimetry up to 1 Terapascal. These results nearly double the highest pressure at which extended x-ray absorption fine structure has been reported in any material. In this work, the copper temperature is unexpectedly found to be much higher than predicted when adjacent to diamond layer(s), demonstrating the important influence of the sample environment on the thermal state of materials; this effect may introduce additional temperature uncertainties in some previous experiments using diamond and provides new guidance for future experimental design.
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The collisionless ion-Weibel instability is a leading candidate mechanism for the formation of collisionless shocks in many astrophysical systems, where the typical distance between particle collisions is much larger than the system size. Multiple laboratory experiments aimed at studying this process utilize laser-driven (Iâ³10^{15} W/cm^{2}), counterstreaming plasma flows (Vâ²2000 km/s) to create conditions unstable to Weibel-filamentation and growth. This technique intrinsically produces temporally varying plasma conditions at the midplane of the interaction where Weibel-driven B fields are generated and studied. Experiments discussed herein demonstrate robust formation of Weibel-driven B fields under multiple plasma conditions using CH, Al, and Cu plasmas. Linear theory based on benchmarked radiation-hydrodynamic FLASH calculations is compared with Fourier analyses of proton images taken â¼5-6 linear growth times into the evolution. The new analyses presented here indicate that the low-density, high-velocity plasma-conditions present during the first linear-growth time (â¼300-500 ps) sets the spectral characteristics of Weibel filaments during the entire evolution. It is shown that the dominant wavelength (â¼300µm) at saturation persists well into the nonlinear phase, consistent with theory under these experimental conditions. However, estimates of B-field strength, while difficult to determine accurately due to the path-integrated nature of proton imaging, are shown to be in the â¼10-30 T range, an order of magnitude above the expected saturation limit in homogenous plamas but consistent with enhanced B fields in the midplane due to temporally varying plasma conditions in experiments.
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Plastic deformation of samples compressed to Mbar pressures at high strain rates at the National Ignition Facility (NIF) forms the basis of ongoing material strength experiments in conditions relevant to meteor impacts, geophysics, armor development, and inertial confinement fusion. Hard x-ray radiography is the primary means of measuring the evolution of these samples, typically employing a slit-collimated high-Z microdot driven by the NIF laser to generate >40 keV x rays [E. Gumbrell et al., Rev. Sci. Instrum. 89, 10G118 (2018) and C. M. Huntington et al., Rev. Sci. Instrum. 89, 10G121 (2018)]. Alternatively, a dysprosium "micro-flag" target driven by the Advanced Radiographic Capability laser (â¼2 kJ, 10 ps) can deliver significantly higher spatiotemporal resolution [M. P. Hill et al., Rev. Sci. Instrum. 92, 033535 (2021)], especially in high-opacity samples. Initial experiments revealed problematic brightness and spectral gradients from this source, but by radiographing a set of diamond-turned, 105 µm-thick Pb test objects and supported by simulations using the 3D Monte Carlo code GEANT4, these geometry-dependent gradients across the field of view are quantified and mitigation strategies are assessed. In addition to significantly enhancing the modulation transfer function compared to the existing system, image stacking from multiple layers of image plate is shown to almost double the signal to noise ratio that will reduce uncertainties in future dynamic strength experiments.
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Psychosocial counseling is the foundation of genetic counseling. Genetic counseling students are required to receive in-depth training on psychosocial counseling techniques. In other medical disciplines, "medical improv," an educational method derived from improvisational theatre, has been used to allow trainees to practice clinical skills without also having to focus on medical knowledge they've not yet mastered. The present study aims to investigate the acceptability of medical improv as an educational tool for genetic counseling students. Fourteen genetic counseling students and new genetic counselors completed a 2-hr medical improv workshop and participated in follow-up interviews to discuss the workshop. Participants' responses to the intervention were positive, with 92.9% of participants responding that they would recommend medical improv training to other genetic counseling students. Participants described the medical improv workshop as helping build psychosocial skills in a safe environment, which may facilitate the use of more advanced counseling skills in clinical situations. By training students to practice psychosocial skills and building students' confidence, medical improv may help genetic counseling students and genetic counselors be more effective in challenging clinical situations, and to feel more comfortable in experimenting with new ideas and psychosocial techniques in their clinical practice.
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Asesoramiento Genético , Estudiantes de Medicina , Competencia Clínica , Consejo , Curriculum , Asesoramiento Genético/psicología , Humanos , Estudiantes , Estudiantes de Medicina/psicologíaRESUMEN
Achieving a high conversion efficiency into relativistic electrons is central to short-pulse laser application and fundamentally relies on creating interaction regions with intensities â«10^{18}W/cm^{2}. Small focal length optics are typically employed to achieve this goal; however, this solution is impractical for large kJ-class systems that are constrained by facility geometry, debris concerns, and component costs. We fielded target-mounted compound parabolic concentrators to overcome these limitations and achieved nearly an order-of-magnitude increase to the conversion efficiency and more than tripled electron temperature compared to flat targets. Particle-in-cell simulations demonstrate that plasma confinement within the cone and formation of turbulent laser fields that develop from cone wall reflections are responsible for the improved laser-to-target coupling. These passive target components can be used to improve the coupling efficiency for all high-intensity short-pulse laser applications, particularly at large facilities with long focal length optics.
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Radiography of low-contrast features in high-density materials evolving on a nanosecond timescale requires a bright photon source in the tens of keV range with high temporal and spatial resolution. One application for sources in this category is the study of dynamic material strength in samples compressed to Mbar pressures at the National Ignition Facility, high-resolution measurements of plastic deformation under conditions relevant to meteor impacts, geophysics, armor development, and inertial confinement fusion. We present radiographic data and the modulation transfer function (MTF) analysis of a multi-component test object probed at â¼100 keV effective backlighter energy using a 5 µm-thin dysprosium foil driven by the NIF Advanced Radiographic Capability (ARC) short-pulse laser (â¼2 kJ, 10 ps). The thin edge of the foil acts as a bright line-projection source of hard x rays, which images the test object at 13.2× magnification into a filtered and shielded image plate detector stack. The system demonstrates a superior contrast of shallow (5 µm amplitude) sinusoidal ripples on gold samples up to 90 µm thick as well as enhanced spatial and temporal resolution using only a small fraction of the laser energy compared to an existing long-pulse-driven backlighter used routinely at the NIF for dynamic strength experiments.
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Laser compression has long been used as a method to study solids at high pressure. This is commonly achieved by sandwiching a sample between two diamond anvils and using a ramped laser pulse to slowly compress the sample, while keeping it cool enough to stay below the melt curve. We demonstrate a different approach, using a multilayer 'ring-up' target whereby laser-ablation pressure compresses Pb up to 150 GPa while keeping it solid, over two times as high in pressure than where it would shock melt on the Hugoniot. We find that the efficiency of this approach compares favourably with the commonly used diamond sandwich technique and could be important for new facilities located at XFELs and synchrotrons which often have higher repetition rate, lower energy lasers which limits the achievable pressures that can be reached.
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Precise dosing of warfarin is important to achieve therapeutic benefit without adverse effects. Pharmacogenomics explains some interindividual variability in warfarin response, but less attention has been paid to drug-drug interactions in the context of genetic factors. We investigated retrospectively the combined effects of cytochrome P450 (CYP)2C9 and vitamin K epoxide reductase complex (VKORC)1 genotypes and concurrent exposure to CYP2C9-interacting drugs on long-term measures of warfarin anticoagulation. Study participants predicted to be sensitive responders to warfarin based on CYP2C9 and VKORC1 genotypes, had significantly greater international normalized ratio (INR) variability over time. Participants who were concurrently taking CYP2C9-interacting drugs were found to have greater INR variability and lesser time in therapeutic range. The associations of INR variability with genotype were driven by the subgroup not exposed to interacting drugs, whereas the effect of interacting drug exposure was driven by the subgroup categorized as normal responders. Our findings emphasize the importance of considering drug interactions in pharmacogenomic studies.
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Anticoagulantes/farmacocinética , Fibrilación Atrial/tratamiento farmacológico , Citocromo P-450 CYP2C9/genética , Vitamina K Epóxido Reductasas/genética , Warfarina/farmacocinética , Anciano , Anticoagulantes/administración & dosificación , Coagulación Sanguínea/efectos de los fármacos , Citocromo P-450 CYP2C9/metabolismo , Relación Dosis-Respuesta a Droga , Interacciones Farmacológicas/genética , Femenino , Humanos , Relación Normalizada Internacional , Masculino , Persona de Mediana Edad , Variantes Farmacogenómicas , Estudios Retrospectivos , Vitamina K Epóxido Reductasas/metabolismo , Warfarina/administración & dosificaciónRESUMEN
Relativistic electron temperatures were measured from kilojoule, subrelativistic laser-plasma interactions. Experiments show an order of magnitude higher temperatures than expected from a ponderomotive scaling, where temperatures of up to 2.2 MeV were generated using an intensity of 1×10^{18}W/cm^{2}. Two-dimensional particle-in-cell simulations suggest that electrons gain superponderomotive energies by stochastic acceleration as they sample a large area of rapidly changing laser phase. We demonstrate that such high temperatures are possible from subrelativistic intensities by using lasers with long pulse durations and large spatial scales.
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We study the high-pressure strength of Pb and Pb-4wt%Sb at the National Ignition Facility. We measure Rayleigh-Taylor growth of preformed ripples ramp compressed to â¼400 GPa peak pressure, among the highest-pressure strength measurements ever reported on any platform. We find agreement with 2D simulations using the Improved Steinberg-Guinan strength model for body-centered-cubic Pb; the Pb-4wt%Sb alloy behaves similarly within the error bars. The combination of high-rate, pressure-induced hardening and polymorphism yield an average inferred flow stress of â¼3.8 GPa at high pressure, a â¼250-fold increase, changing Pb from soft to extremely strong.
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We present molecular dynamics simulations of shock and release in micron-scale tantalum crystals that exhibit postbreakout temperatures far exceeding those expected under the standard assumption of isentropic release. We show via an energy-budget analysis that this is due to plastic-work heating from material strength that largely counters thermoelastic cooling. The simulations are corroborated by experiments where the release temperatures of laser-shocked tantalum foils are deduced from their thermal strains via in situ x-ray diffraction and are found to be close to those behind the shock.
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A high speed solid-state framing camera has been developed which can operate in interferometric mode. This camera measures the change in the index of refraction of a semiconductor when x-rays are incident upon it. This instrument uses an x-ray transmission grating/mask in front of the semiconductor to induce a corresponding phase grating in the semiconductor which can then be measured by an infrared probe beam. The probe beam scatters off of this grating, enabling a measure of the x-ray signal incident on the semiconductor. In this particular instrument, the zero-order reflected probe beam is attenuated and interfered with the diffracted orders to produce an interferometric image on a charge coupled device camera of the phase change induced inside the semiconductor by the incident x-rays.
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Extended X-ray absorption fine structure (EXAFS) spectroscopy is a powerful tool for in situ characterization of matter in the high energy density regime. An EXAFS platform is currently being developed on the National Ignition Facility. Development of a suitable X-ray backlighter involves minimizing the temporal duration and source size while maximizing spectral smoothness and brightness. One approach involves imploding a spherical shell, which generates a high-flux X-ray flash at stagnation. We present results from a series of experiments comparing the X-ray source properties produced by imploded empty and Ar-filled capsules.
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We have used femtosecond x-ray diffraction to study laser-shocked fiber-textured polycrystalline tantalum targets as the 37-253 GPa shock waves break out from the free surface. We extract the time and depth-dependent strain profiles within the Ta target as the rarefaction wave travels back into the bulk of the sample. In agreement with molecular dynamics simulations, the lattice rotation and the twins that are formed under shock compression are observed to be almost fully eliminated by the rarefaction process.
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Energy-transport effects can alter the structure that develops as a supernova evolves into a supernova remnant. The Rayleigh-Taylor instability is thought to produce structure at the interface between the stellar ejecta and the circumstellar matter, based on simple models and hydrodynamic simulations. Here we report experimental results from the National Ignition Facility to explore how large energy fluxes, which are present in supernovae, affect this structure. We observed a reduction in Rayleigh-Taylor growth. In analyzing the comparison with supernova SN1993J, a Type II supernova, we found that the energy fluxes produced by heat conduction appear to be larger than the radiative energy fluxes, and large enough to have dramatic consequences. No reported astrophysical simulations have included radiation and heat conduction self-consistently in modeling supernova remnants and these dynamics should be noted in the understanding of young supernova remnants.
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Magnetic fields are ubiquitous in the Universe. The energy density of these fields is typically comparable to the energy density of the fluid motions of the plasma in which they are embedded, making magnetic fields essential players in the dynamics of the luminous matter. The standard theoretical model for the origin of these strong magnetic fields is through the amplification of tiny seed fields via turbulent dynamo to the level consistent with current observations. However, experimental demonstration of the turbulent dynamo mechanism has remained elusive, since it requires plasma conditions that are extremely hard to re-create in terrestrial laboratories. Here we demonstrate, using laser-produced colliding plasma flows, that turbulence is indeed capable of rapidly amplifying seed fields to near equipartition with the turbulent fluid motions. These results support the notion that turbulent dynamo is a viable mechanism responsible for the observed present-day magnetization.
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Quantitative risk assessment (QRA) for food allergens has made considerable progress in recent years, yet acceptability of its outcomes remains stymied because of the limited extent to which it has been possible to incorporate severity as a variable. Reaction severity, particularly following accidental exposure, depends on multiple factors, related to the allergen, the host and any treatments, which might be administered. Some of these factors are plausibly still unknown. Quantitative risk assessment shows that limiting exposure through control of dose reduces the rates of reactions in allergic populations, but its impact on the relative frequency of severe reactions at different doses is unclear. Food challenge studies suggest that the relationship between dose of allergenic food and reaction severity is complex even under relatively controlled conditions. Because of these complexities, epidemiological studies provide very limited insight into this aspect of the dose-response relationship. Emerging data from single-dose challenges suggest that graded food challenges may overestimate the rate of severe reactions. It may be necessary to generate new data (such as those from single-dose challenges) to reliably identify the effect of dose on severity for use in QRA. Success will reduce uncertainty in the susceptible population and improve consumer choice.
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Alérgenos/inmunología , Hipersensibilidad a los Alimentos/epidemiología , Hipersensibilidad a los Alimentos/inmunología , Alimentos/efectos adversos , Reacciones Cruzadas , Europa (Continente)/epidemiología , Hipersensibilidad a los Alimentos/diagnóstico , Humanos , Inmunización , Medición de Riesgo , Factores de Riesgo , Índice de Severidad de la EnfermedadRESUMEN
BACKGROUND: Nut allergy varies from pollen cross-allergy, to primary severe allergy with life-threatening symptoms. The screening of IgE antibodies to a wide spectrum of allergens, including species-specific and cross-reactive allergens, is made possible via microarray analysis. OBJECTIVE: We sought to study the association of variable IgE sensitization profiles to clinical response in peanut-challenged children and adolescents in a birch-endemic region. In addition, we studied the avoidance of tree nuts and species-specific sensitizations. METHODS: We studied 102 peanut-sensitized patients who underwent a double-blind placebo-controlled challenge to peanut. We analysed ISAC ImmunoCAP microarray to 112 allergens, singleplex ImmunoCAPs for hazelnut Cor a 14 and cashew Ana o 3, and performed skin prick tests to peanut, tree nuts and sesame seed. We surveyed avoidance diets with a questionnaire. RESULTS: Sensitization to PR-10 proteins was frequent (Bet v 1 90%), but equally high in the challenge negatives and positives. IgE to Ara h 2 and Ara h 6 discriminated peanut allergic (n = 69) and tolerant (n = 33) the best. Avoidance of tree nuts was common (52% to 96%), but only 6% to 44% presented species-specific sensitizations to tree nuts, so a great number could potentially introduce these species into their diet. CONCLUSIONS AND CLINICAL RELEVANCE: PR-10-sensitizations were frequent and strong regardless of peanut allergy status. Component-resolved diagnostics can be employed to demonstrate to patients that sensitization to seed storage proteins of tree nuts is uncommon. Several tree nuts could potentially be reintroduced to the diet.
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Arachis/efectos adversos , Dieta , Nueces/inmunología , Hipersensibilidad al Cacahuete/diagnóstico , Hipersensibilidad al Cacahuete/inmunología , Alérgenos/inmunología , Antígenos de Plantas/inmunología , Biomarcadores , Reacciones Cruzadas/inmunología , Femenino , Humanos , Inmunoglobulina E/inmunología , Masculino , Pruebas CutáneasRESUMEN
The development and introduction of new dietary protein sources has the potential to improve food supply sustainability. Understanding the potential allergenicity of these new or modified proteins is crucial to ensure protection of public health. Exposure to new proteins may result in de novo sensitization, with or without clinical allergy, or clinical reactions through cross-reactivity. In this paper we review the potential of current methodologies (in silico, in vitro degradation, in vitro IgE binding, animal models and clinical studies) to address these outcomes for risk assessment purposes for new proteins, and especially to identify and characterise the risk of sensitization for IgE mediated allergy from oral exposure. Existing tools and tests are capable of assessing potential crossreactivity. However, there are few possibilities to assess the hazard due to de novo sensitization. The only methods available are in vivo models, but many limitations exist to use them for assessing risk. We conclude that there is a need to understand which criteria adequately define allergenicity for risk assessment purposes, and from these criteria develop a more suitable battery of tests to distinguish between proteins of high and low allergenicity, which can then be applied to assess new proteins with unknown risks.
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Proteínas en la Dieta/efectos adversos , Hipersensibilidad a los Alimentos/inmunología , Inmunoglobulina E/inmunología , Alérgenos/inmunología , Animales , Reacciones Cruzadas , Proteínas en la Dieta/inmunología , Alimentos Modificados Genéticamente , Humanos , Modelos Animales , Medición de RiesgoRESUMEN
Pressure-driven shock waves in solid materials can cause extreme damage and deformation. Understanding this deformation and the associated defects that are created in the material is crucial in the study of a wide range of phenomena, including planetary formation and asteroid impact sites, the formation of interstellar dust clouds, ballistic penetrators, spacecraft shielding and ductility in high-performance ceramics. At the lattice level, the basic mechanisms of plastic deformation are twinning (whereby crystallites with a mirror-image lattice form) and slip (whereby lattice dislocations are generated and move), but determining which of these mechanisms is active during deformation is challenging. Experiments that characterized lattice defects have typically examined the microstructure of samples after deformation, and so are complicated by post-shock annealing and reverberations. In addition, measurements have been limited to relatively modest pressures (less than 100 gigapascals). In situ X-ray diffraction experiments can provide insights into the dynamic behaviour of materials, but have only recently been applied to plasticity during shock compression and have yet to provide detailed insight into competing deformation mechanisms. Here we present X-ray diffraction experiments with femtosecond resolution that capture in situ, lattice-level information on the microstructural processes that drive shock-wave-driven deformation. To demonstrate this method we shock-compress the body-centred-cubic material tantalum-an important material for high-energy-density physics owing to its high shock impedance and high X-ray opacity. Tantalum is also a material for which previous shock compression simulations and experiments have provided conflicting information about the dominant deformation mechanism. Our experiments reveal twinning and related lattice rotation occurring on the timescale of tens of picoseconds. In addition, despite the common association between twinning and strong shocks, we find a transition from twinning to dislocation-slip-dominated plasticity at high pressure (more than 150 gigapascals), a regime that recovery experiments cannot accurately access. The techniques demonstrated here will be useful for studying shock waves and other high-strain-rate phenomena, as well as a broad range of processes induced by plasticity.